The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling.
The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling.
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广泛使用的 Wnt1-Cre 转基因通过异位激活 Wnt 信号传导导致发育表型。
DOI：
10.1016/j.ydbio.2013.04.026
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发表时间：
2013-07-15
影响因子：
2.7
通讯作者：
Bush, Jeffrey O.
中科院分区：
文献类型：
--
作者：
Lewis, Ace E.;Vasudevan, Harish N.;O'Neill, Audrey K.;Soriano, Philippe;Bush, Jeffrey O.
Wnt 1-Cre转基因小鼠系广泛用于神经嵴及其衍生物和中脑发育的研究。Wnt 1基因在中脑-后脑边界的形成、中脑大小的调节和腹侧中脑多巴胺能神经元的发生中具有重要的发育作用。在这里，我们报告，Wnt 1-Cre转基因小鼠表现出中脑发育的多个方面的表型。中脑的显著扩张和发育中下丘的增殖增加与Wnt 1的异位表达相关。腹侧中脑中Wnt 1表达的显著升高与腹侧mDA神经元分化程序的中断相关。我们发现这些表型可以归因于Wnt 1-Cre转基因的Wnt 1异位表达，导致经典Wnt/β-catenin信号转导的异位激活。由于这些警告可能会使Wnt 1-Cre在某些发育情况下的效用复杂化，因此我们报告了一种新的Wnt 1-Cre 2转基因小鼠系，该系可以与原始小鼠达到相同的目的，而没有相关的表型并发症。这些研究揭示了广泛使用的试剂的一个重要警告，提供了该试剂的改进版本，并表明原始Wnt 1-Cre转基因小鼠系可用作询问中脑发育多个方面的Wnt信号传导机制的功能模型的增益。
The Wnt1-Cre transgenic mouse line is extensively used in the study of the development of the neural crest and its derivatives and the midbrain. The Wnt1 gene has important developmental roles in formation of the midbrain–hindbrain boundary, regulation of midbrain size, and neurogenesis of ventral midbrain dopaminergic (mDA) neurons. Here, we report that Wnt1-Cre transgenic mice exhibit phenotypes in multiple aspects of midbrain development. Significant expansion of the midbrain and increased proliferation in the developing inferior colliculus is associated with ectopic expression of Wnt1. Marked elevation of Wnt1 expression in the ventral midbrain is correlated with disruption of the differentiation program of ventral mDA neurons. We find that these phenotypes can be attributed to ectopic expression of Wnt1 from the Wnt1-Cre transgene leading to the ectopic activation of canonical Wnt/β-catenin signaling. Since these caveats could complicate the utility of Wnt1-Cre in some developmental circumstances, we report a new Wnt1-Cre2 transgenic mouse line that can serve the same purposes as the original without the associated phenotypic complications. These studies reveal an important caveat to a widely-used reagent, provide an improved version of this reagent, and indicate that the original Wnt1-Cre transgenic mouse line may be useful as a gain of function model for interrogating Wnt signaling mechanisms in multiple aspects of midbrain development.
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影响因子：
4.6
作者：
Tang, Mianzhi;Miyamoto, Yasunori;Huang, Eric J.
通讯作者：
Huang, Eric J.
影响因子：
2.6
作者：
Yoshida, Toshiyuki;Vivatbutsiri, Philaiporn;Iseki, Sachiko
通讯作者：
Iseki, Sachiko
影响因子：
4.6
作者：
Ito, Y;Yeo, JY;Chai, Y
通讯作者：
Chai, Y
影响因子：
2.7
作者：
Jiang, XB;Iseki, S;Morriss-Kay, GM
通讯作者：
Morriss-Kay, GM
影响因子：
64.8
作者：
Danielian, PS;McMahon, AP
通讯作者：
McMahon, AP